Adaptor protein HIP-55 promotes macrophage M1 polarization through promoting AP-1 complex activation.

Overwhelming macrophage M1 polarization induced by malfunction of the renin-angiotensin-aldosterone system (RAAS) initiates inflammatory responses, which play a crucial role in various cardiovascular diseases. However, the underlying regulatory mechanism remains elusive. Here, we identified adaptor protein HIP-55 as a critical regulator of macrophage M1 polarization.

Nanoparticles Internalization through HIP-55-Dependent Clathrin Endocytosis Pathway.

Nanoparticles are promising tools for biomedicine. Many nanoparticles are internalized to function. Clathrin-mediated endocytosis is one of the most important mechanisms for nanoparticle internalization.

Posttranslational modifications in GPCR internalization.

G protein-coupled receptors (GPCRs) are the largest family of membrane receptors that serve as the most important drug targets. Classically, GPCR internalization has been considered to lead to receptor desensitization. However, many studies over the past decade have reported that internalized membrane receptors can trigger distinct signal activation.

The new fate of internalized membrane receptors: Internalized activation.

Classically, the fate of internalized membrane receptors includes receptor degradation and receptor recycling. However, recent findings have begun to challenge these views. Much research demonstrated that many internalized membrane receptors can trigger distinct signal activation rather than being desensitized inside the cell.

Internalized Activation of Membrane Receptors: From Phenomenon to Theory.

Many studies over the past decade have reported that internalized membrane receptors can trigger distinct signal activation, rather than being desensitized inside the cell. Here, we propose the concept of 'internalized activation' as a distinctive component of the receptor theory framework and exhibit its significance and role in diseases.

Angiotensin-converting enzyme 2 (ACE2): SARS-CoV-2 receptor and RAS modulator.

The coronavirus disease 2019 (COVID-19) outbreak is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) was rapidly identified as the critical functional receptor for SARS-CoV-2. ACE2 is well-known as a counter-regulator of the renin-angiotensin system (RAS) and plays a key role in the cardiovascular system.

Increased ATR expression is induced by ATR autoantibody via two axes, Klf-5/IRF-1 and circErbB4/miR-29a-5p, to promote VSMC migration.

Vascular remodeling can be caused by angiotensin II type 1 receptor (ATR) autoantibody (AT1-AA), although the related mechanism remains unknown. Angiotensin II type 2 receptor (ATR) plays multiple roles in vascular remodeling through cross-talk with ATR in the cytoplasm. Here, we aimed to explore the role and mechanism of ATR in AT1-AA-induced vascular smooth muscle cell (VSMC) migration, which is a key event in vascular remodeling.

Autoantibodies against AT1 Receptor Contribute to Vascular Aging and Endothelial Cell Senescence.

Vascular aging predisposes the elderly to the progression of many aging-related vascular disorders and leads to deterioration of cardiovascular diseases (CVD). However, the underlying mechanisms have not been clearly elucidated. Agonistic autoantibodies against angiotensin II type 1 (AT1) receptor (AT1-AAs) have been demonstrated to be pro-inflammatory and contribute to the progression of atherosclerosis.

Limited AT1 Receptor Internalization Is a Novel Mechanism Underlying Sustained Vasoconstriction Induced by AT1 Receptor Autoantibody From Preeclampsia.

Background Angiotensin II type 1 receptor ( AT R) autoantibody ( AT 1- AA ) was first identified as a causative factor in preeclampsia. Unlike physiological ligand angiotensin II (Ang II ), AT 1- AA can induce vasoconstriction in a sustained manner, causing a series of adverse effects, such as vascular injury and poor placental perfusion. However, its underlying mechanisms remain unclear.

Active immunization using hand-push emulsification method increases the operator's risk of transcutaneous immunization.

Setting up an animal model by using active immunization methods is a common means of studying immune-related diseases or producing antibodies with high titer and high activities. However, the security during the process of pathogen emulsification remains unclear. In a physical examination, we unexpectedly noticed high levels of angiotensin II type 1 receptor autoantibody (AT1-AA) specific to the immunizing antigen in the sera of some researchers who had participated in setting up active immunization animal models, and we were puzzled about the cause of AT1-AA production.

[Angiotensin II type 1 receptor autoantibody induces myocardial fibrosis by activating cardiac fibroblasts].

Myocardial fibrosis (MF) is an important pathological process of cardiac remodeling in patients with heart failure; however its etiology has not been clear. It has been known that the angiotensin II type 1 receptor autoantibody (AT1-AA) is present in patients with heart failure, but it is unclear whether this antibody directly causes MF. In this study, we investigated the role of AT1-AA in MF and its effects on cardiac fibroblasts (CFs).

The inhibitory effect of BKCa channels induced by autoantibodies against angiotensin II type 1 receptor is independent of AT1R.

Autoantibodies against angiotensin II Type 1 receptor (AT1-AA) are routinely detected in the serum of preeclampsia patients, which results in an increase in vascular tone and an elevation in intracellular calcium concentration of rat vascular smooth muscle (VSM). The big conductance calcium-activated potassium channels (BKCa channels) account for the dominant outward currents in VSMCs, contributing to membrane hyperpolarization and vasodilation. In the present study, we investigated the effect of AT1-AA on BKCa channels.

Effects of methamphetamine abuse on spatial cognitive function.

Methamphetamine (MA) abuse has been rising rapidly over the past decade, however, its impact in spatial cognitive function remains unknown. To understand its effect on visuospatial ability and spatial orientation ability, 40 MA users and 40 non-MA users conducted the Simple Reaction Task (Task 1), the Spatial Orientation Task (Task 2), and the Mental Rotation Task (Task 3), respectively. There was no significant difference in either accuracy or reaction time (RT) between 2 groups in Task 1.

The mechanisms behind decreased internalization of angiotensin II type 1 receptor.

The internalization of angiotensin II type 1 receptor (ATR) plays an important role in maintaining cardiovascular homeostasis. Decreased receptor internalization is closely related to cardiovascular diseases induced by the abnormal activation of ATR, such as hypertension. However, the mechanism behind reduced ATR internalization is not fully understood.

Long-term presence of angiotensin II type 1 receptor autoantibody reduces aldosterone production by triggering Ca overload in H295R cells.

Preeclamptic women are reported to have inadequate plasma volume expansion coupled with a suppressed secretion of aldosterone; however, the specific mechanism of preeclampsia remains unclear. We demonstrated that the presence of long-term angiotensin II type 1 receptor autoantibody (AT1-AA) reduces aldosterone production by triggering a Ca overload in H295R cells. AT1-AA was discovered in preeclamptic women and reported to activate ATR, and consequently elevate intracellular Ca.